MOLECULAR BIOLOGY OF VARICELLA-ZOSTER VIRUS INFECTIONS

水痘-带状疱疹病毒(VZV)的初次感染会导致水痘，以及 从潜伏期重新激活病毒会导致带状疱疹。的目标 该项目旨在鉴定和确定VZV基因的功能 在活动性感染和体内潜伏期表达。 我们目前正在研究调节VZV基因的功能 病毒基因表达。急性发作期VZV基因产物分析 感染表明至少有5个VZV基因，ORF4，ORF10，ORF61， ORF62和ORF63反式激活VZV其他基因的表达 体外培养。其中两个基因(ORFlO、ORF62)直接激活转录 并确定了它们的活化域。其中三个VZV 基因(ORF110、ORF61和ORF62)可以补充其功能 单纯疱疹病毒的同源基因，而其中一个基因(ORF4)不能。 含有部分VZV蛋白及其HSV-1的嵌合蛋白 同系物，已经被构建来比较这些功能域 蛋白质。 两个VZV基因ORF28和ORF29具有双向重叠的启动子 来调节它们的表达。这些控制元素通过以下方式激活 一种病毒蛋白(ORF62)和一种称为USF的细胞蛋白。虽然这两个人 这些基因在急性感染中都有表达，其中一个基因(ORF29)是 而另一个基因(ORF28)则不表达。 无活动性证据的人身体三叉神经节分析 表明至少有两个VZV基因(ORF29和ORF62) 在病毒潜伏期间表达，而其他基因(ORF110、ORF28和 ORF61)不是。

Primary infection with varicella-zoster virus (VZV) causes chickenpox, and reactivation of the virus from latency results in zoster. The goals of this project are to identify and determine the function of VZV genes that are expressed during active infection and during latency in the body. We are currently investigating the functions of VZV genes that regulate viral gene expression. Analysis of VZV gene products during acute infection indicate that at least five VZV genes, ORF4, ORF1O, ORF6l, ORF62, and ORF63, transactivate the expression of other VZV genes in vitro. Two of these genes (ORFlO, ORF62) activate transcription directly and their activation domains have been identified. Three of these vzv genes (ORF1O, ORF61, and ORF62) can complement the function of their herpes simplex virus homologs, while one of the genes (ORF4) cannot. Chimeric proteins, containing portions of VZV proteins and their HSV-1 homologs, have been constructed to compare functional domains of these proteins. Two VZV genes, ORF28 and ORF29, have bidirectional, overlapping promoters that regulate their expression. These control elements are activated by a viral protein (ORF62) and a cellular protein termed USF. While both of these genes are expressed in acute infection, one of the genes (ORF29) is expressed during dormant infection, while the other gene (ORF28) is not. Analysis of trigeminal ganglia from human cadavers without active evidence of VZV infection indicates that at least two VZV genes (ORF29 and ORF62) are expressed during viral latency, while other genes (ORF1O, ORF28, and ORF61) are not.